A new version of the integrase inhibitor cabotegravir has been developed into a nanoformulated prodrug that could soon be a once-yearly treatment for people living with HIV-1, according to recent research in Nature Materials.
Although results have only been tested in mice and rhesus macaques, “This pharmaceutical development has the potential to not only treat but also prevent viral transmission,” Howard E. Gendelman, MD, professor of internal medicine and infectious diseases chair in the department of pharmaceutical sciences at the University of Nebraska Medical Center in Omaha, said in a press release. “This may certainly be a therapeutic milestone.”
Currently, cabotegravir (ViiV Healthcare; Research Triangle, NC) is being investigated as a long-acting injectable for the treatment of HIV-1 and for use as pre-exposure prophylaxis (PrEP). While cabotegravir’s injectable form expands antiretroviral therapy from a daily to monthly treatment, barriers to treatment success with long-acting cabotegravir in patients living with HIV include adverse reactions to injections and frequent visits to healthcare services.
Gendelman and colleagues sought to modify cabotegravir as a way to overcome some of these limitations. They created a nanocrystal prodrug formulation of cabotegravir with poloxamer-coated hydrophobic and lipophilic surfactants, testing the extended release potential of three candidates in lab animals.
The researchers found the nanoformulated prodrug version of cabotegravir slowly released the drug in both mice and rhesus macaques. “This occurs for extended time periods, and in laboratory and animal testing, up to a year,” Benson J. Edagwa, PhD, of the department of pharmacology and experimental neuroscience at the University of Nebraska Medical Center, said in a press release. One candidate, NM2CAB, had “prolonged drug release, plasma circulation time and tissue drug concentrations after a single 45 mg per kg body weight intramuscular injection,” the researchers said.
The researchers have suggested that the nanoformulated prodrug version of cabotegravir could be more effective than the current monthly injectable version and could even become a vaccine mimetic for HIV-1. “While viral vaccines and long-acting modified ARVs have very different modes of action, they can both function to protect against infection,” Gendelman said.
Gendelman, who is also the interim director of the Nebraska Nanomedicine Production Plant, said the team plans to develop the cabotegravir prodrug into a potential treatment for patients living with and those at risk of developing HIV-1.
